Jacobson Moriah L, Wulf Hildegard A, Browne Caroline A, Lucki Irwin
Department of Pharmacology and Molecular Therapeutics, Uniformed Service University, Bethesda, MD, United States.
Department of Pharmacology and Molecular Therapeutics, Uniformed Service University, Bethesda, MD, United States.
Prog Brain Res. 2018;239:1-48. doi: 10.1016/bs.pbr.2018.07.007. Epub 2018 Sep 18.
The failure of traditional antidepressant medications to adequately target cognitive impairment is associated with poor treatment response, increased risk of relapse, and greater lifetime disability. Opioid receptor antagonists are currently under development as novel therapeutics for major depressive disorder (MDD) and other stress-related illnesses. Although it is known that dysregulation of the endogenous opioid system is observed in patients diagnosed with MDD, the impact of opioidergic neurotransmission on cognitive impairment has not been systematically evaluated. Here we review the literature indicating that opioid manipulations can alter cognitive functions in humans. Furthermore, we detail the preclinical studies that demonstrate the ability of mu-opioid receptor and kappa-opioid receptor ligands to modulate several cognitive processes. Specifically, this review focuses on domains within higher order cognitive processing, including attention and executive functioning, which can differentiate cognitive processes influenced by motivational state.
传统抗抑郁药物未能充分针对认知障碍，这与治疗反应不佳、复发风险增加以及更高的终生残疾率相关。阿片受体拮抗剂目前正在作为治疗重度抑郁症（MDD）和其他应激相关疾病的新型疗法进行研发。虽然已知在被诊断为MDD的患者中观察到内源性阿片系统失调，但阿片能神经传递对认知障碍的影响尚未得到系统评估。在此，我们回顾了表明阿片类药物操作可改变人类认知功能的文献。此外，我们详细介绍了临床前研究，这些研究证明了μ-阿片受体和κ-阿片受体配体调节多种认知过程的能力。具体而言，本综述重点关注高阶认知加工中的领域，包括注意力和执行功能，这些领域可以区分受动机状态影响的认知过程。
